Properties of receptors for the Ca2+-channel blocker verapamil in transverse-tubule membranes of skeletal muscle. Stereospecificity, effect of Ca2+ and other inorganic cations, evidence for two categories of sites and effect of nucleoside triphosphates.
Properties of receptors for the Ca2+-channel blocker verapamil in transverse-tubule membranes of skeletal muscle. Stereospecificity, effect of Ca2+ and other inorganic cations, evidence for two categories of sites and effect of nucleoside triphosphates.
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骨骼肌横管膜中 Ca2 通道阻滞剂维拉帕米受体的特性。
DOI：
10.1111/j.1432-1033.1984.tb08451.x
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
M. Lazdunski
中科院分区：
文献类型：
--
作者：
J. Galizzi;M. Fosset;M. Lazdunski
与兔骨骼肌横管膜电压依赖性钙通道相关的维拉帕米受体具有以下特性。(I)该受体具有立体特异性，可区分维拉帕米、加洛帕米和地尔硫卓的不同立体异构体。(Ii)无机二价阳离子以一种明显的非竞争性方式抑制[~3H]维拉帕米与其受体的结合。效价顺序为：Ca2+=Mn2+>Mg2+>Sr2+>Ba2+>Co2+>Ni2+。Ca~(2+)和Mn~(2+)的抑制常数为0.3 mM。[~3H]维拉帕米与Cs~+、K~+、Li~+、Na~+等单价阳离子的结合也很敏感。其中活性最强的阳离子(Cs+和K+)的抑制常数在30 mM范围内。(Iii)[~3H]维拉帕米的结合是pH依赖的，揭示了维拉帕米受体上存在一个必需的电离基团，pKa为6.5。(4)通过对维拉帕米受体的解离动力学的研究，发现了维拉帕米和其他一些钙通道阻滞剂的低亲和力结合部位。(V)GTP和核苷类似物改变了[~3H]维拉帕米与维拉帕米结合部位的性质。高亲和力结合部位似乎转移到低亲和力部位。通过对[~3H]维拉帕米结合的抑制研究，得到了GTP、ATP和GPP(NH)p的解离常数在0.1-0.3 mM范围内。
The verapamil receptor associated with the voltage-dependent calcium channel of rabbit skeletal muscle transverse tubule membranes has the following properties. (i) This receptor is stereospecific and discriminates between the different stereoisomers of verapamil, gallopamil and diltiazem. (ii) Inorganic divalent cations inhibit the binding of [3H]verapamil to its receptor in an apparently non-competitive fashion. The rank order of potency is: Ca2+ = Mn2+ greater than Mg2+ greater than Sr2+ greater than Ba2+ much greater than Co2+ much greater than Ni2+. Ca2+ and Mn2+ have inhibition constants of 0.3 mM. Binding of [3H]verapamil is also sensitive to monovalent cations such as Cs+, K+, Li+ and Na+. The most active of these cations (Cs+ and K+) have inhibition constants in the range of 30 mM. (iii) Binding of [3H]verapamil is pH-dependent and reveals the presence on the verapamil receptor of an essential ionizable group with a pKa of 6.5. (iv) A low-affinity binding site for verapamil and for some other Ca2+ channel blockers is detected by studies of dissociation kinetics of the [3H]verapamil receptor in the presence of high concentrations of verapamil, gallopamil, bepridil and diltiazem. (v) GTP and nucleoside analogs change the properties of [3H]verapamil binding to verapamil binding sites. High-affinity binding sites seem to be transferred into low-affinity sites. Dissociation constants obtained from inhibition studies of [3H]verapamil binding are in the range of 0.1-0.3 mM for GTP, ATP and Gpp(NH)p.
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DOI：
--
发表时间：
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